tbuckley/cabot-search huggingface dataset:
Dual-endoscopy detection for an esophageal-jejunal anastomotic fistula
Authors: Zhengying Yang, Ying Bi, Jinfeng Ren, Xihui Yuan, Neng Wang, Tianyu Liu
Journal: Endoscopy (2023)

An anastomotic fistula is a severe complication of post-gastrectomy. In the past, re-surgery has been the most common method to address this complication [1]. However, it may bring many subsequent complications [2]. With the development of endoscopic techniques and related accessories, endoscopy is gradually able to address more post-surgical complications. Here, we report a case of dual-endoscopy detection and suture of an esophageal-jejunal anastomosis fistula.
Adjuvant immunotherapy with nivolumab versus observation in completely resected Merkel cell carcinoma (ADMEC-O): disease-free survival results from a randomised, open-label, phase 2 trial
Authors: Jürgen C Becker, Selma Ugurel, Ulrike Leiter, Friedegund Meier, Ralf Gutzmer, Sebastian Haferkamp, Lisa Zimmer, Elisabeth Livingstone, Thomas K Eigentler, Axel Hauschild, Felix Kiecker, Jessica C Hassel, Peter Mohr, Michael Fluck, Ioannis Thomas, Marlene Garzarolli, Imke Grimmelmann, Konstantin Drexler, Alexandra N Spillner, Sebastian Eckhardt, Dirk Schadendorf, Alexander van Akkooi, Winan van Houdt, Tabea Wilhelm, Kimberley Farmer, Claas Ulrich, Thilo Gambichler, Leonie Bluhm, Heidemarie Schinagl, Ivonne Kellner, Rudolf Herbst, Frank Meiß, David Rafei-Shamsabadi, Sabine Sell, Martin Kaatz, Lena Wulfken, Martin Hartmann, Katharina Kähler, Mirjana Ziemer, Jan Simon, Patrick Terheyden, Diamant Thaci, Carmen Loquai, Heidrun Mitzel-Rink, Stephan Grabbe, Henner Stege, Maria Gaiser, Jochen Utikal, Carola Berking, Lucie Heinzerling, Max Schlaak, Dirk Tomsitz, Jörg Dyballa, Nina Magnolo, Carsten Weishaupt, Mark Berneburg, Claus Garbe, Lukas Flatz, Anja Gesierich, Bastian Schilling
Journal: The Lancet (2023)
Targeting the metabolism of tumor-infiltrating regulatory T cells
Authors: Yiming Wang, Tianning Huang, Jian Gu, Ling Lu
Journal: Trends in Immunology (2023)

Although targeting the tumor metabolism is performed in cooperation with immunotherapy in the era of precision oncology, ignorance of immune cells' metabolism has resulted in unstable antitumor responses. Tumor-infiltrating regulatory T cells (TI-Tregs) are unique, overcoming the hypoxic, acidic, and nutrient-deficient tumor microenvironments (TMEs) and maintaining immunosuppressive functions. However, secondary autoimmunity caused by systemic Treg depletion remains the 'Sword of Damocles' for current Treg-targeted therapies. In this opinion piece, we propose that metabolically reprogrammed TI-Tregs might represent an obstacle to cancer therapies. Indeed, metabolism-based Treg-targeted therapy might provide higher selectivity for clearing TI-Tregs than traditional kinase/checkpoint inhibitors and chemokine/chemokine receptor blockade; it might also restore the efficacy of targeting the tumor metabolism and eliminate certain metabolic barriers to immunotherapy.
A Pilot Randomized Trial of an Advance Care Planning Video Decision Support Tool for Adolescents and Young Adults With Advanced Cancer
Authors: Jennifer M. Snaman, Deborah Feifer, Gabrielle Helton, Yuchiao Chang, Areej El-Jawahri, Angelo E. Volandes, Joanne Wolfe
Journal: Journal of the National Comprehensive Cancer Network (2023)

Background: Adolescents and young adults (AYAs) with advanced cancer often receive intensive end-of-life care, yet it is unclear if this is goal-concordant. Advance care planning (ACP) video tools may promote identification and communication of AYA preferences. Patients and Methods: We conducted a dual-site, 1:1 pilot randomized controlled trial of a novel video-based ACP tool in 50 dyads of AYA patients aged 18 to 39 years with advanced cancer and their caregivers. ACP readiness and knowledge, preferences for future care, and decisional conflict were obtained pre, post, and 3 months after the intervention and compared between groups. Results: Of the 50 AYA/caregiver dyads enrolled, 25 (50%) were randomized to the intervention. Participants primarily identified as female, white, and non-Hispanic. Most AYAs (76%) and caregivers (86%) identified their overall goal as life-prolonging preintervention; less identified this goal postintervention (42% AYAs; 52% caregivers). There was no significant difference in change in proportion of AYAs or caregivers choosing life-prolonging care, CPR, or ventilation between arms postintervention or at 3 months. The change in participant scores for ACP knowledge (AYAs and caregivers) and ACP readiness (AYAs) from preintervention to postintervention was greater in the video arm compared with the control arm; the difference in caregivers’ scores for decisional conflict from preintervention to postintervention in the video arm was statistically significant (15 vs 7; P =.005). Feedback from the video participants was overwhelmingly positive; of the 45 intervention participants who provided video feedback, 43 (96%) found the video helpful, 40 (89%) were comfortable viewing the video, and 42 (93%) indicated they would recommend the video to other patients facing similar decisions. Conclusions: Most AYAs with advanced cancer and their caregivers preferred life-prolonging care in advanced illness, with fewer preferring this type of care postintervention. A brief video-based ACP tool was well-liked by participants and improved caregiver decisional certainty. Videos may be a useful tool to inform AYAs and caregivers about end-of-life care options and promote ACP discussions.
Therapy for Stage IV Non–Small-Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2023.2
Authors: Dwight H. Owen, Navneet Singh, Nofisat Ismaila, Gregory Masters, Gregory J. Riely, Andrew G. Robinson, Bryan J. Schneider, Ishmael A. Jaiyesimi
Journal: Journal of Clinical Oncology (2023)

Living guidelines are developed for selected topic areas with rapidly evolving evidence that drives frequent change in clinical practice. Living guidelines are updated on a regular schedule by a standing expert panel that systematically reviews the health literature on a continuous basis; as described in theASCO Guidelines Methodology Manual. ASCO Living Guidelines follow theASCO Conflict of Interest Policy Implementation for Clinical Practice Guidelines. Living Guidelines and updates are not intended to substitute for independent professional judgment of the treating provider and do not account for individual variation among patients. See appendix for disclaimers and other important information (Appendix 1 and Appendix 2). Updates are published regularly and can be found athttps://ascopubs.org/nsclc-da-living-guideline.
Painfully Absent
Authors: Suzanne Broens, Frederique H. van Duijnhoven, Markus W. Hollmann, Sabrine N.T. Hemmes
Journal: Journal of Clinical Oncology (2023)

With great interest we read the study by Badwe et al 1 investigating the effect of peritumoral injection of lidocaine before breast cancer surgery on survival and cancer recurrence.We would like to commend our colleagues with their great achievement in completing this large trial with lengthy follow-up.The authors provide a relevant contribution to the current controversial evidence on the effect of local anesthetics on metastatic spread of breast cancer.However, in our opinion, important aspects of perioperative analgesia were insufficiently addressed: the systemic effect of lidocaine and the effect on the surgical stress response and perioperative pain.
Helen Salisbury: Physician associates in general practice
Authors: Helen Salisbury
Journal: BMJ (2023)

Last week, the tragic and avoidable death of a young woman was discussed in parliament. 1 The patient had presented to her general practice with, reportedly, obvious symptoms of a deep vein thrombosis and a pulmonary embolus.This diagnosis was not made then, nor after her condition worsened and she returned a week later.She died a few hours after this second visit.
Glycemic Measures in Childhood as Predictors of Future Diabetes-Related Microvascular Complications in an Indigenous American Population
Authors: Laura Vazquez, Elsa Vazquez Arreola, Robert L. Hanson, Madhumita Sinha
Journal: Diabetes Care (2023)

To examine the role of glycemic measures performed during childhood in predicting future diabetes-related nephropathy and retinopathy in a high-risk indigenous American cohort.
The Association Between Age at Diagnosis and Disease Characteristics and Damage in Patients With <scp>ANCA‐Associated</scp> Vasculitis
Authors: Jessica L. Bloom, Kaci Pickett‐Nairn, Lori Silveira, Robert C. Fuhlbrigge, David Cuthbertson, Praveen Akuthota, Thomas C. Corbridge, Nader A. Khalidi, Curry L. Koening, Carol A. Langford, Carol A. McAlear, Paul A. Monach, Larry W. Moreland, Christian Pagnoux, Rennie L. Rhee, Philip Seo, Jared Silver, Ulrich Specks, Kenneth J. Warrington, Michael E. Wechsler, Peter A. Merkel
Journal: Arthritis & Rheumatology (2023)

Objective This study examined the relationship between age at diagnosis and disease characteristics and damage in patients with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV). Methods Analysis of a prospective longitudinal cohort of patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic GPA (EGPA) in the Vasculitis Clinical Research Consortium (2013–2021). Disease cohorts were divided by age at diagnosis (years): children (&lt;18), young adults (18–40), middle‐aged adults (41–65), and older adults (&gt;65). Data included demographics, ANCA type, clinical characteristics, Vasculitis Damage Index (VDI) scores, ANCA Vasculitis Index of Damage (AVID) scores, and novel disease‐specific and non‐disease‐specific damage scores built from VDI and AVID items. Results Analysis included data from 1020 patients with GPA/MPA and 357 with EGPA. Female predominance in GPA/MPA decreased with age at diagnosis. AAV in childhood was more often GPA and proteinase 3‐ANCA positive. Children with GPA/MPA experienced more subglottic stenosis and alveolar hemorrhage; children and young adults with EGPA experienced more alveolar hemorrhage, need for intubation, and gastrointestinal involvement. Older adults (GPA/MPA) had more neurologic manifestations. After adjusting for disease duration, medications, tobacco, and ANCA, all damage scores increased with age at diagnosis for GPA/MPA ( P &lt; 0.001) except the disease‐specific damage score, which did not differ ( P = 0.44). For EGPA, VDI scores increased with age at diagnosis ( P &lt; 0.009), whereas all other scores were not significantly different. Conclusion Age at diagnosis is associated with clinical characteristics in AAV. Although VDI and AVID scores increase with age at diagnosis, this is driven by non‐disease‐specific damage items. image
Cardiovascular Implications of Vascular Endothelial Growth Factor Inhibition Among Adolescents/Young Adults in ECOG-ACRIN E2805
Authors: Wendy J. Bottinor, Yael Flamand, Naomi B. Haas, Anne M. ONeill, Robert S. DiPaola, Pearl Subramanian, David Cella, W. Gregory Hundley, Lynne I. Wagner, John M. Salsman, Bonnie Ky
Journal: Journal of the National Comprehensive Cancer Network (2023)

Background: Cardiovascular disease (CVD) is a leading cause of morbidity and mortality among adolescents and young adults (AYAs) diagnosed with cancer. The aim of this study was to assess the incidence and predictors of left ventricular systolic dysfunction (LVSD) and hypertension among AYAs receiving VEGF inhibition compared with non-AYAs. Methods: This retrospective analysis used data from the ASSURE trial (ClinicalTrials.gov identifier: NCT00326898 ), in which participants with nonmetastatic, high-risk, renal cell cancer were randomized to sunitinib, sorafenib, or placebo. The incidence of LVSD (left ventricular ejection fraction decrease &gt;15%) and hypertension (blood pressure ≥140/90 mm Hg) were compared using nonparametric tests. Multivariable logistic regression examined the association between AYA status, LVSD, and hypertension while adjusting for clinical factors. Results: AYAs represented 7% (103/1,572) of the population. Over a study treatment period of 54 weeks, the incidence of LVSD was not significantly different among AYAs (3%; 95% CI, 0.6%–8.3%) versus non-AYAs (2%; 95% CI, 1.2%–2.7%). The incidence of hypertension was significantly lower among AYAs (18%; 95% CI, 7.5%–33.5%) compared with non-AYAs (46%; 95% CI, 41.9%–50.4%) in the placebo arm. In the sunitinib and sorafenib groups, the incidence of hypertension for AYAs compared with non-AYAs was 29% (95% CI, 15.1%–47.5%) versus 47% (95% CI, 42.3%–51.7%), and 54% (95% CI, 33.9%–72.5%) versus 63% (95% CI, 58.6%–67.7%), respectively. AYA status (odds ratio, 0.48; 95% CI, 0.31–0.75) and female sex (odds ratio, 0.74; 95% CI, 0.59–0.92) were each associated with a lower risk of hypertension. Conclusions: LVSD and hypertension were prevalent among AYAs. CVD among AYAs is only partially explained by cancer therapy. Understanding CVD risk among AYA cancer survivors is important for promoting cardiovascular health in this growing population.
NCCN Guidelines® Insights: Biliary Tract Cancers, Version 2.2023
Authors: Al B. Benson, Michael I. D’Angelica, Thomas Abrams, Daniel E. Abbott, Aijaz Ahmed, Daniel A. Anaya, Robert Anders, Chandrakanth Are, Melinda Bachini, David Binder, Mitesh Borad, Christopher Bowlus, Daniel Brown, Adam Burgoyne, Jason Castellanos, Prabhleen Chahal, Jordan Cloyd, Anne M. Covey, Evan S. Glazer, William G. Hawkins, Renuka Iyer, Rojymon Jacob, Lawrence Jennings, R. Kate Kelley, Robin Kim, Matthew Levine, Manisha Palta, James O. Park, Steven Raman, Sanjay Reddy, Sean Ronnekleiv-Kelly, Vaibhav Sahai, Gagandeep Singh, Stacey Stein, Anita Turk, Jean-Nicolas Vauthey, Alan P. Venook, Adam Yopp, Nicole McMillian, Ryan Schonfeld, Cindy Hochstetler
Journal: Journal of the National Comprehensive Cancer Network (2023)

In 2023, the NCCN Guidelines for Hepatobiliary Cancers were divided into 2 separate guidelines: Hepatocellular Carcinoma and Biliary Tract Cancers. The NCCN Guidelines for Biliary Tract Cancers provide recommendations for the evaluation and comprehensive care of patients with gallbladder cancer, intrahepatic cholangiocarcinoma, and extrahepatic cholangiocarcinoma. The multidisciplinary panel of experts meets at least on an annual basis to review requests from internal and external entities as well as to evaluate new data on current and emerging therapies. These Guidelines Insights focus on some of the recent updates to the NCCN Guidelines for Biliary Tract Cancers as well as the newly published section on principles of molecular testing.
Metastasis Unleashed: Hyposialylation Empowers Chemo-Evasive Circulating Tumor Cell Clusters in Breast Cancer
Authors: Ana Gvozdenovic, Nicola Aceto
Journal: Cancer Research (2023)

Abstract Therapy resistance is frequently observed in cancer patients with distant metastases and effective management of metastatic disease remains challenging. Unraveling the cellular mechanisms and molecular targets fueling metastatic spread is crucial for advancing cancer therapies. In a recent issue of Cancer Discovery, Dashzeveg and colleagues revealed that loss of terminal sialylation in glycoproteins within circulating tumor cell clusters is a dynamic process that contributes to cellular dormancy, facilitates evasion of chemotherapy, and enhances metastatic seeding. Furthermore, the study identifies the glycoprotein podocalyxin (PODXL) as a potential target for counteracting the metastasis of quiescent tumor cells associated with paclitaxel treatment in triple-negative breast cancer.
Intraperitoneal Paclitaxel Is a Safe and Effective Therapeutic Strategy for Treating Mucinous Appendiceal Adenocarcinoma
Authors: Ichiaki Ito, Abdelrahman M.G. Yousef, Saikat Chowdhury, Princess N. Dickson, Zahra A. Naini, Michael G. White, Karianne G. Fleten, Kjersti Flatmark, Keith F. Fournier, Natalie W. Fowlkes, John Paul Shen
Journal: Cancer Research (2023)

Abstract Appendiceal adenocarcinomas (AA) are a rare and heterogeneous mix of tumors for which few preclinical models exist. The rarity of AA has made performing prospective clinical trials difficult, which has partly contributed to AA remaining an orphan disease with no chemotherapeutic agents approved by the FDA for its treatment. AA has a unique biology in which it frequently forms diffuse peritoneal metastases but almost never spreads via a hematogenous route and rarely spreads to lymphatics. Given the localization of AA to the peritoneal space, intraperitoneal delivery of chemotherapy could be an effective treatment strategy. Here, we tested the efficacy of paclitaxel given by intraperitoneal administration using three orthotopic patient-derived xenograft (PDX) models of AA established in immunodeficient NSG mice. Weekly intraperitoneal paclitaxel treatment dramatically reduced AA tumor growth in all three PDX models. Comparing the safety and efficacy of intravenous with intraperitoneal administration, intraperitoneal delivery of paclitaxel was more effective, with reduced systemic side effects in mice. Given the established safety record of intraperitoneal paclitaxel in gastric and ovarian cancers, and lack of effective chemotherapeutics for AA, these data showing the activity of intraperitoneal paclitaxel in orthotopic PDX models of mucinous AA support the evaluation of intraperitoneal paclitaxel in a prospective clinical trial. Significance: The activity and safety of intraperitoneal paclitaxel in orthotopic PDX models of mucinous appendiceal adenocarcinoma supports the evaluation of intraperitoneal paclitaxel in a prospective clinical trial of this rare tumor type.
Intratumoral Microbiota Composition Regulates Chemoimmunotherapy Response in Esophageal Squamous Cell Carcinoma
Authors: Hong Wu, Xuefeng Leng, Qianshi Liu, Tianqin Mao, Tao Jiang, Yiqiang Liu, Feifei Li, Chenhui Cao, Jun Fan, Liang Chen, Yaqi Chen, Quan Yao, Shun Lu, Renchuan Liang, Lanlin Hu, Mingxin Liu, Yejian Wan, Zhaoshen Li, Jun Peng, Qiyu Luo, Hang Zhou, Jun Yin, Ke Xu, Mei Lan, Xinhao Peng, Haitao Lan, Gang Li, Yongtao Han, Xia Zhang, Zhi-Xiong Jim Xiao, Jinyi Lang, Guihua Wang, Chuan Xu
Journal: Cancer Research (2023)

Abstract Neoadjuvant chemoimmunotherapy (NACI) has shown promise in the treatment of resectable esophageal squamous cell carcinoma (ESCC). The microbiomes of patients can impact therapy response, and previous studies have demonstrated that intestinal microbiota influences cancer immunotherapy by activating gut immunity. Here, we investigated the effects of intratumoral microbiota on the response of patients with ESCC to NACI. Intratumoral microbiota signatures of β-diversity were disparate and predicted the treatment efficiency of NACI. The enrichment of Streptococcus positively correlated with GrzB+ and CD8+ T-cell infiltration in tumor tissues. The abundance of Streptococcus could predict prolonged disease-free survival in ESCC. Single-cell RNA sequencing demonstrated that responders displayed a higher proportion of CD8+ effector memory T cells but a lower proportion of CD4+ regulatory T cells. Mice that underwent fecal microbial transplantation or intestinal colonization with Streptococcus from responders showed enrichment of Streptococcus in tumor tissues, elevated tumor-infiltrating CD8+ T cells, and a favorable response to anti-PD-1 treatment. Collectively, this study suggests that intratumoral Streptococcus signatures could predict NACI response and sheds light on the potential clinical utility of intratumoral microbiota for cancer immunotherapy. Significance: Analysis of intratumoral microbiota in patients with esophageal cancer identifies a microbiota signature that is associated with chemoimmunotherapy response and reveals that Streptococcus induces a favorable response by stimulating CD8+ T-cell infiltration. See related commentary by Sfanos, p. 2985
Constitutional MLH1 Methylation Is a Major Contributor to Mismatch Repair–Deficient, MLH1-Methylated Colorectal Cancer in Patients Aged 55 Years and Younger
Authors: Megan P. Hitchins, Estela Dámaso, Rocio Alvarez, Lisa Zhou, Yajing Hu, Marcio A. Diniz, Marta Pineda, Gabriel Capella, Rachel Pearlman, Heather Hampel
Journal: Journal of the National Comprehensive Cancer Network (2023)

Most mismatch repair-deficient (MMRd) colorectal cancer (CRC) cases arise sporadically, associated with somatic MLH1 methylation, whereas approximately 20% have germline mismatch repair pathogenic variants causing Lynch syndrome (LS). Universal screening of incident CRC uses presence of MLH1 methylation in MMRd tumors to exclude sporadic cases from germline testing for LS. However, this overlooks rare cases with constitutional MLH1 methylation (epimutation), a poorly recognized mechanism for LS. We aimed to assess the frequency and age distribution of constitutional MLH1 methylation among incident CRC cases with MMRd, MLH1-methylated tumors.In retrospective population-based studies, we selected all CRC cases with MMRd, MLH1-methylated tumors, regardless of age, prior cancer, family history, or BRAF V600E status, from the Columbus-area HNPCC study (Columbus) and Ohio Colorectal Cancer Prevention Initiative (OCCPI) cohorts. Blood DNA was tested for constitutional MLH1 methylation by pyrosequencing and real-time methylation-specific PCR, then confirmed with bisulfite-sequencing.Results were achieved for 95 of 98 Columbus cases and all 281 OCCPI cases. Constitutional MLH1 methylation was identified in 4 of 95 (4%) Columbus cases, ages 34, 38, 52, and 74 years, and 4 of 281 (1.4%) OCCPI cases, ages 20, 34, 50, and 55 years, with 3 showing low-level mosaic methylation. Mosaicism in blood and normal colon, plus tumor loss of heterozygosity of the unmethylated allele, demonstrated causality in 1 case with sample availability. Age stratification showed high rates of constitutional MLH1 methylation among younger patients. In the Columbus and OCCPI cohorts, respectively, these rates were 67% (2 of 3) and 25% (2 of 8) of patients aged <50 years but with half of the cases missed, and 75% (3 of 4) and 23.5% (4 of 17) of patients aged ≤55 years with most cases detected.Although rare overall, a significant proportion of younger patients with MLH1-methylated CRC had underlying constitutional MLH1 methylation. Routine testing for this high-risk mechanism is warranted in patients aged ≤55 years for a timely and accurate molecular diagnosis that will significantly alter their clinical management while minimizing additional testing.